Considerable evidence indicates an etiological role for HTLV-III and related retroviruses in the current epidemic of AIDS. The env gene-coded proteins of retroviruses play important roles in the biological activities of these agents, and are the major targets of the protective immune response against these viruses. We have considerable experience in the characterization of the structure, functional activities, and immunological pro-erties of the env gene products of the murine leukemia viruses, which represent an excellent retrovirus model for understanding the recent human isolates such as HTLV-III. We propose to perform similar characterizations of the AIDS virus env components. Monoclonal antibodies will be prepared against the purified glycoproteins of HTLV-III and LAV. The localization and chemical nature of the epitopes on the env proteins recognized by these antibodies antibodies will be studied, and the neutralizing and cytotoxic titers of the antibodies determined, as means of identifying those sites on the env proteins which induce such activities. A binding competition assay will be developed as an efficient method of characterizing similar activities in sera of human subjects exposed to the AIDS viruses. Using appropriate antisera, the biosynthesis of the env gene products will be characterized, the contribution of carbohydrates to the maturation and function of these proteins will be determined, and the subunit organization of the env components will be elucidated. The effect of the purified HTLV-III env proteins on in vitro hematopoietic cell differentiation and functional activities will be determined. These studies should provide needed insight into the nature of these molecules which should clarify their functional roles in induction of AIDS, and which should facilitate the design of an effective vaccine against these viruses.